Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients

  1. Arne Sattler
  2. Eva Schrezenmeier
  3. Ulrike A. Weber
  4. Alexander Potekhin
  5. Friederike Bachmann
  6. Henriette Straub-Hohenbleicher
  7. Klemens Budde
  8. Elena Storz
  9. Vanessa Proß
  10. Yasmin Bergmann
  11. Linda M.L. Thole
  12. Caroline Tizian
  13. Oliver Hölsken
  14. Andreas Diefenbach
  15. Hubert Schrezenmeier
  16. Bernd Jahrsdörfer
  17. Tomasz Zemojtel
  18. Katharina Jechow
  19. Christian Conrad
  20. Sören Lukassen
  21. Diana Stauch
  22. Nils Lachmann
  23. Mira Choi
  24. Fabian Halleck
  25. Katja Kotsch

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Abstract

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  1. Version published to 10.1172/jci150175
  2. ScreenIT

    SciScore for 10.1101/2021.04.06.21254963: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The blocking ELISA based assay qualitatively detects anti-SARS-CoV2 antibodies inhibiting the interaction between receptor binding domain (RBD) of the viral spike glycoprotein and angiotensin-converting enzyme.
    anti-SARS-CoV2
    suggested: None
    Flow cytometric analysis: For detection of surface molecules, antibodies against CD3 (SK7, Biolegend, Carlsbad, CA, USA), CD4 (SK3, Becton Dickinson, Franklin Lakes, NJ, USA)
    CD3
    suggested: None
    CD4
    suggested: None
    Software and Algorithms
    SentencesResources
    Following adapter trimming, alignment to the GRCh38 reference genome obtained from ENSEMBL (38) was performed using STAR 2.7.1a (39) retaining only properly paired, uniquely mapping reads.
    ENSEMBL
    suggested: (Ensembl, RRID:SCR_002344)
    STAR
    suggested: (STAR, RRID:SCR_004463)
    Count matrices were generated using featureCounts from subread 2.0.1 (40) with annotation version GRCh38.98 obtained from ENSEMBL.
    featureCounts
    suggested: (featureCounts, RRID:SCR_012919)
    Downstream processing was performed using DESeq2 1.22.2 (41) in R 3.5.1.
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    Differentially regulated pathways between groups were determined by Gene Set Enrichment Analysis (GSEA 4.1.0, (
    GSEA
    suggested: (SeqGSEA, RRID:SCR_005724)
    FACS data analysis: FACS data were analyzed with FlowJo 10 (Becton Dickinson).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Unsupervised analysis was conducted using t-distributed stochastic neighbor embedding (t-SNE) included in Cytobank (Beckman Coulter, Krefeld, Germany).
    Cytobank
    suggested: (Cytobank, RRID:SCR_014043)
    Statistics: Statistical examination and composition of ELISA and FACS data derived graphs were executed using GraphPad Prism 8 (GraphPad, La Jolla, CA, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Using comprehensive multiparameter analysis, our data further reveal significant limitations of vaccine-specific Th effector functions in these individuals, applying to all cytokines examined and equally affecting polyfunctionality. T cells secreting multiple effector molecules at a time have gained particular attention due to their association with superior viral control in HIV infected subjects (23) that was further verified for influenza infection (24). In context with vaccination, multipotent Th cells have been correlated with vaccine-induced immunity against tuberculosis (25). The presence of virus-reactive, multipotent T cells in convalescent seronegative individuals suggests a comparable role in protection against SARS-CoV2 (26), with possible implications for its absence in KTx patients. Extending flow cytometric data, low input transcriptome analysis of vaccine-specific T helper cells from transplant recipients highlighted downregulation of pathways involved in e.g. cellular activation, cytokine signalling and metabolism. Not surprisingly, these hallmarks represent footprints of immunosuppressive medication, as was e.g. shown for impaired IL-2-STAT5 signalling post kidney transplantation (27). Interestingly, IL-2 gene activity is also sensitive to TGFβ signalling (28), reflecting one of the features we found upregulated in Th cells from KTx patients. Amongst single genes, TNFSF4 (OX40L) showed increased transcript levels in this patient group; of note, OX40L protein ...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 27. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.04.06.21254963v1 on medRxiv